Biphasic responses of equine colonic vessel rings to vasoactive inflammatory mediators.
Abstract: 1. The role of endothelium in modulating equine colonic vessel responses to histamine (HST), 5-hydroxytryptamine (5-HT), bradykinin (BK) and acetylcholine (ACh) was evaluated in vitro. 2. Segments of mesenteric arteries and veins were collected from the left ventral colon of six adult horses destined for euthanasia for reasons unrelated to cardiovascular or gastrointestinal systems. Vessels were gently cleansed and cut into 4 mm wide rings. 3. Three vessel conditions namely endothelium intact, endothelium removed and N omega-nitro-L-arginine methyl ester (L-NAME)-treated were used for both arterial and venous rings. Each ring was placed in an organ bath with oxygenated Tyrode's solution. One side of the ring was fixed to the floor of the bath and the other side to a force-displacement transducer interfaced with a polygraph. 4. An initial tension of 2 g was applied to rings which were allowed to equilibrate for 45 min. The bath solution was gently replaced every 15 min and tension was readjusted to 2 g each time except following the last wash. 5. Rings were precontracted with a single EC25 dose of noradrenaline and after the response plateaued, cumulative concentration (10(-12)-10(-4) M) response curves were determined for each agent on separate rings. The relaxation from the precontracted level to the baseline was considered as 100% relaxation. Maximal relaxation and maximal contractions were statistically analyzed. 6. All agents induced a relaxation response initially, followed by a contractile phase as the concentrations increased in both arteries and veins, thus, making a biphasic concentration-response curve. In arteries, relaxation produced by ACh was significantly greater than 5-HT. Endothelium removal and L-NAME treatment significantly reduced relaxation in arteries. Only endothelium removal produced a significant reduction of relaxation in veins. 7. In both arteries and veins, HST and 5-HT produced significantly greater contraction than ACh or BK. No significant change in contraction was observed in arteries either by endothelium removal or L-NAME treatment, however, contraction was significantly reduced in veins by endothelium removal. 8. These findings suggest that the endothelium plays a major role in modulating equine colonic arterial relaxation via nitric oxide and venous contraction via endothelium-derived contractile mediators, probably endothelin and/or arachidonates.
Publication Date: 1998-10-27 PubMed ID: 9788293DOI: 10.1046/j.1365-2680.1998.18488.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This study evaluates the role of the endothelium in regulating how horse colonic vessels respond to stimuli such as histamine (HST), 5-hydroxytryptamine (5-HT), bradykinin (BK) and acetylcholine (ACh). Results show that all test agents initiated a relaxation response initially, followed by a contractile phase as the concentrations increased. It also found that the endothelium significantly influences horse colonic arterial relaxation and venous contraction.
Research Methodology
- The study was conducted using mesenteric arteries and veins extracted from the left ventral colony of six adult horses that were on the path for euthanasia due to reasons uncorrelated to cardiovascular or gastrointestinal issues.
- These vessels were carefully cleansed and cut into 4 mm wide rings and were subjected to three conditions – endothelium intact, endothelium removed, and treatment with N omega-nitro-L-arginine methyl ester (L-NAME).
- The rings were placed in an organ bath with oxygenated Tyrode’s solution, affixed to a force-displacement transducer linked to a polygraph. 2 g of initial tension was applied, and the solution was replaced every 15 min with the tension readjusted to 2 g.
- Then the rings were precontracted with a single EC25 dose of noradrenaline, and concentration-response curves were determined for each test agent on separate rings.
Findings and Results
- All test agents initiated a relaxation response first, followed by a contractile phase as the concentrations increased, creating a biphasic concentration-response curve. The level of relaxation produced by ACh in arteries was significantly more than by 5-HT.
- Results also showed that removal of the endothelium and treatment with L-NAME notably reduced relaxation in arteries, though only the removal of the endothelium showed a significant reduction of relaxation in veins.
- In both arteries and veins, HST and 5-HT led to greater contraction than ACh or BK. No significant difference in contraction was observed in arteries either by endothelium removal or L-NAME treatment, however, contraction was significantly reduced in veins by the removal of the endothelium.
Conclusion
- Overall, these findings suggest that the endothelium plays a vital role in modulating equine colonic arterial relaxation via nitric oxide and venous contraction via endothelium-derived contractile factors, probably endothelin and/or arachidonates.
Cite This Article
APA
Venugopalan CS, Moore RM, Holmes EP, Sedrish SA, Koch CE.
(1998).
Biphasic responses of equine colonic vessel rings to vasoactive inflammatory mediators.
J Auton Pharmacol, 18(4), 231-237.
https://doi.org/10.1046/j.1365-2680.1998.18488.x Publication
Researcher Affiliations
- Department of Veterinary Physiology, Pharmacology & Toxicology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.
MeSH Terms
- Acetylcholine / pharmacology
- Animals
- Bradykinin / pharmacology
- Colon / blood supply
- Endothelium, Vascular / drug effects
- Endothelium, Vascular / physiology
- Enzyme Inhibitors / pharmacology
- Histamine / pharmacology
- Horses
- In Vitro Techniques
- Muscle Relaxation / drug effects
- Muscle, Smooth, Vascular / drug effects
- Muscle, Smooth, Vascular / physiology
- NG-Nitroarginine Methyl Ester / pharmacology
- Nitric Oxide Synthase / antagonists & inhibitors
- Serotonin / pharmacology
- Vasodilator Agents / pharmacology
Citations
This article has been cited 2 times.- Stokes AM, Venugopal CS, Hosgood G, Eades SC, Moore RM. Comparison of 2 endothelin-receptor antagonists on in vitro responses of equine palmar digital arterial and venous rings to endothelin-1.. Can J Vet Res 2006 Jul;70(3):197-205.
- Moore RM, Sedrish SA, Holmes EP, Koch CE, Venugopal CS. Role of endothelium and nitric oxide in modulating in vitro responses of colonic arterial and venous rings to vasodilatory neuropeptides in horses.. Can J Vet Res 2005 Apr;69(2):116-22.
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